Indian Medicinal Plants and Formulations and Their Potential Against COVID-19-Preclinical and Clinical Research
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REVIEW
published: 02 March 2021
doi: 10.3389/fphar.2020.578970
Indian Medicinal Plants and
Formulations and Their Potential
Against COVID-19–Preclinical and
Clinical Research
Sayeed Ahmad 1†*, Sultan Zahiruddin 1†, Bushra Parveen 1†, Parakh Basist 1, Abida Parveen 2,
Gaurav 1, Rabea Parveen 3 and Minhaj Ahmad 4
1
Bioactive Natural Product Laboratory, Department of Pharmacognosy and Phytochemistry, School of Pharmaceutical Education
and Research, Jamia Hamdard (Deemed University), New Delhi, India, 2Centre for Translational and Clinical Research, Jamia
Hamdard (Deemed University), New Delhi, India, 3Department of Biosciences, Jamia Millia Islamia (Central University), New Delhi,
India, 4Department of Surgery, School of Unani Medical Education and Research, Jamia Hamdard (Deemed University), New
Delhi, India
The cases of COVID-19 are still increasing day-by-day worldwide, even after a year of its
Edited by: first occurrence in Wuhan city of China. The spreading of SARS-CoV-2 infection is very fast
Michael Heinrich, and different from other SARS-CoV infections possibly due to structural differences in S
UCL School of Pharmacy,
proteins. The patients with severe diseases may die due to acute respiratory distress
United Kingdom
syndrome (ARDS) caused by systemic inflammatory reactions due to the excessive release
Reviewed by:
Shailendra Shivaji Gurav, of pro-inflammatory cytokines and chemokines by the immune effector cells. In India too, it
Goa College of Pharmacy, India is spreading very rapidly, although the case fatality rate is below 1.50% (https://www.
Subhash Chandra Mandal,
Directorate of Drugs Control, India
statista.com), which is markedly less than in other countries, despite the dense population
*Correspondence:
and minimal health infrastructure in rural areas. This may be due to the routine use of many
Sayeed Ahmad immunomodulator medicinal plants and traditional AYUSH formulations by the Indian
sahmad_jh@yahoo.co.in
people. This communication reviews the AYUSH recommended formulations and their
†
These authors have contributed
ingredients, routinely used medicinal plants and formulations by Indian population as well
equally to this work
as other promising Indian medicinal plants, which can be tested against COVID-19.
Specialty section: Special emphasis is placed on Indian medicinal plants reported for antiviral,
This article was submitted to immunomodulatory and anti-allergic/anti-inflammatory activities and they are
Ethnopharmacology,
a section of the journal categorized for prioritization in research on the basis of earlier reports. The traditional
Frontiers in Pharmacology AYUSH medicines currently under clinical trials against COVID-19 are also discussed as
Received: 01 July 2020 well as furtherance of pre-clinical and clinical testing of the potential traditional medicines
Accepted: 29 December 2020
against COVID-19 and SARS-CoV-2. The results of the clinical studies on AYUSH drugs
Published: 02 March 2021
will guide the policymakers from the AYUSH systems of medicines to maneuver their
Citation:
Ahmad S, Zahiruddin S, Parveen B, policies for public health, provide information to the global scientific community and could
Basist P, Parveen A, Gaurav, form a platform for collaborative studies at national and global levels. It is thereby
Parveen R and Ahmad M (2021) Indian
Medicinal Plants and Formulations and suggested that promising AYUSH formulations and Indian medicinal plants must be
Their Potential Against COVID- investigated on a priority basis to solve the current crisis.
19–Preclinical and Clinical Research.
Front. Pharmacol. 11:578970. Keywords: COVID-19, AYUSH medicine, indian medicinal plants, indian traditional medicine, immunomodulators,
doi: 10.3389/fphar.2020.578970 antiviral agents
Frontiers in Pharmacology | www.frontiersin.org 1 March 2021 | Volume 11 | Article 578970Ahmad et al. Indian Medicine against COVID 19
1 INTRODUCTION Although the pathogenesis of COVID-19 is still not clear,
patients with COVID-19 show non-specific symptoms ranging
A novel coronavirus-induced pneumonia, which was later from no symptoms (asymptomatic) to severe pneumonia and
called coronavirus disease 2019 (COVID-19), has rapidly death. However, the most common symptoms include fever,
increased to an epidemic scale and affected whole human non-productive cough, dyspnea, myalgia, fatigue, diarrhea, lung
population globally (WHO, 2020a). In India, the first case damage, normal or decreased leukocyte counts, and radiographic
of COVID-19 was an imported case from Wuhan, China on evidence of pneumonia, which are similar to the symptoms of
January 30, 2020 traced in Kerala (Sahasranaman and Kumar, SARS-CoV and MERS-CoV infections (WHO, 2020b; Rothan and
2020) and the death rate of COVID-19 in India is 1.45%, as of Byrareddy, 2020). Complications include ARDS, acute heart injury,
12th December, 2020 (Worldometers, 2020). Severe acute and secondary infections (Guo et al., 2020).
respiratory syndrome-related coronavirus (SARS-CoV-2) The present conventional strategy of the disease control
has become a pandemic hazard to global public health includes isolation of cases and tracing their contacts, providing
worldwide. optimal care to these infected cases, reducing chances of
Coronaviruses (CoVs) are large viruses comprising of four secondary infections by early diagnosis, and rapid
genera, namely alpha, beta, gamma, and delta. The beta- development of effective diagnostic, preventive and therapeutic
coronavirus class includes severe acute respiratory strategies, including vaccines (WHO, 2020b). The treatment
syndrome (SARS) virus (SARS-CoV), Middle East approach for COVID-19 is supportive care, which is
respiratory syndrome (MERS) virus (MERS-CoV), and the supplemented by the combination of broad-spectrum
COVID-19 causative agent SARS-CoV-2. (Li G. et al., 2020). antibiotics, antivirals, corticosteroids and convalescent plasma
The novel SARS-CoV-2 is a beta CoV that shows 88% (Yang et al., 2020).
similarity to two bat-derived SARS-like CoVs (bat-SL- Scientists are working hard to develop effective treatments. As
CoVZC45 and bat-SL-CoVZXC21), about 50% identical to of October 18, 2020, more than 3611 clinical trials (with more
the sequence of MERSCoV, and 70% similarity in genetic than 100 complementary medicines) on COVID-19 are either
sequence to SARS-CoV (Cheng and Shan, 2020). Although ongoing or enrolling patients, and new ones are being added
there is an extremely high resemblance between SARS-CoV every day, as the case count skyrockets globally. The drugs being
and the novel SARS-CoV-2, the SARS-CoV-2 is spreading tested range from repurposed flu treatments to failed ebola drugs,
rapidly as compared to the SARS-CoV, which may be to malaria treatments that were first developed decades ago
explained by structural differences in the S proteins (Lythgoe and Middleton, 2020). There is scale-up development
(Rabaan et al., 2020). of vaccines across the world by many pharmaceutical companies
The SARS-CoV-2 S protein has been found as a significant as well as research organizations. These treatments undergoing
determinant of virus entry into host cells using angiotensin trials may require months or years to develop and hit the market,
converting enzyme 2 (ACE2) receptor similar to SARS-CoV. meaning that an immediate treatment or control mechanism
Whereas the binding affinity of virion S glycoprotein and ACE2 is should be found, if possible (Table 1).
reported to be 10–20 folds higher in SARS-CoV-2 as compared to Considering the current situation, various treatment modalities
that of SARS-CoV (Song et al., 2018). have been well-thought-out, including traditional medicine, which
Severe cases of COVID-19 are reported to have increased has been widely used during the past epidemic outbreaks, including
plasma concentrations of pro-inflammatory cytokines, including SARS and H1N1 influenza (Luo et al., 2020). Until now three
interleukins (IL-6 and IL-10), tumor necrosis factor (TNF)-α countries including India, China, and South Korea, have issued
granulocyte-colony stimulating factor (G-CSF), monocyte guidelines on traditional regimens for the prevention and
chemoattractant protein 1 (MCP1), and macrophage management of COVID-19 (Ang et al., 2020).
inflammatory protein (MIP)1α (Yuki et al., 2020). Akin to the The Indian Traditional System of Medicine is one of the oldest
common viral infections, the antibody profile against the SARS- systems of medical practice in the world and has played an
CoV virus manifests a typical pattern of IgM and IgG antibody essential role in providing health care service to human
production. The IgG antibody is believed to play a protective role, civilization, right from its inception. India has the exclusive
as the SARS-specific IgG antibodies last for a longer time while distinction of its own recognized traditional medicine;
IgM antibodies disappear at the end of 12 weeks. The latest Ayurveda, Yoga, Unani, Siddha, and Homoeopathy (AYUSH)
reports show a significant reduction in the number of CD4+ (Adhikari and Paul, 2018). These systems are based on definite
and CD8+ T cells in the peripheral blood of SARS-CoV-2-infected medical philosophies and represent a way of achieving a healthy
patients, besides activation of other pro-inflammatory cytokines lifestyle with conventional and established ideas on the
such as nuclear factor-κB (NF-κB), interferon regulatory factor 3 prevention of diseases and the promotion of health. The basic
(IRF3) and type I Interferons (IFN-α/β) (Li G. et al., 2020). A treatment approach of all these systems is holistic and the
recent report shows that many patients died from acute pharmacological modalities are based on natural products of
respiratory distress syndrome (ARDS) caused by the cytokine plants, animals, or mineral origin. Given this, there is a
storm, which is a deadly uncontrolled systemic inflammatory resurgence of interest in AYUSH systems, which have helped
response resulting from the release of large amounts of pro- the nation in the pandemic crisis due to plague, cholera, Spanish
inflammatory cytokines and chemokines by immune effector cells flu, etc. in the past. Hence, by repurposing the traditional uses of
in SARS-CoV infection (Guo et al., 2020). Indian medicinal plants and formulations, new treatment options
Frontiers in Pharmacology | www.frontiersin.org 2 March 2021 | Volume 11 | Article 578970Ahmad et al. Indian Medicine against COVID 19
TABLE 1 | Details of clinical trials completed on AYUSH drugs for COVID-19 (Source: www.ctri.nic.in).
Ctri No./Treatment details Study title Type of trial Remarks
(design of study)
Recruitment status
CTRI/2020/04/024883 ZINGIVIR-H Clinical research on safety and efficacy of Interventional (Other) Zingivir H consumption with standard of
ZingiVir-H as an add on therapy in COVID-19 Completed care in COVID 19 confirmed patients
patients showed a remarkable recovery compared
to that of placebo
CTRI/2020/05/025161/Herbal To study the effectiveness of herbal Interventional (randomized, “Aayudh advance”, when given
formulation-aayudh advance formulation - aayudh advance as a parallel group, active controlled concomitantly with standard of care, was
supplementary treatment for the corona virus Trial) Completed found to be 100% safe, devoid of any drug-
2019 (COVID-19) infected patients drug interaction, effective as virucidal to
reduce viral load, and increased the
recovery rate when compared to standard
of care alone when tested in mild
symptomatic COVID-19 patients
CTRI/2020/05/025215/Kabasura Effectiveness of siddha medicine, kabasura Interventional (randomized, The role of vitamin C with zinc
kudineer kudineer and vitamin c-zinc supplementation parallel group Trial) Completed supplementation in the management of
in the management of mild COVID-19 COVID 19 is still not clear. Therefore, study
patients will compare the effect of kabasura kudineer
and vitamin C with zinc supplementation in
terms of negative conversion of SARS CoV-
2 infection
CTRI/2020/05/025275/Ayurveda Role of chyawanprash in the prevention of Interventional (randomized, No adverse effect was found in the study
rasayana along with conventional COVID-19 in health care workers parallel group Trial) Completed
guidelines for health care workers
CTRI/2020/05/025276/Ayurveda protocol Effect of ayurvedic intervention in COVID-19 Interventional (single arm Trial) Ayurveda treatment protocol includes
positive cases Completed sanshamani, nagaradi kwath, amalaki
churna and golden milk improved the
strength of the patient
CTRI/2020/05/025397/Purified aqueous A study to evaluate the effect and safety of a Interventional (randomized, Clinical improvement was observed in covid
extract of cocculus hirsutus (AQCH) phytopharmaceutical drug in treatment of parallel group Trial) Completed patients in terms of disease severity
coronavirus infection
CTRI/2020/05/025425/Chayapanprash Ayurvedic intervention (chyawanprash) in the Interventional (single arm Trial) This remedy was found to be a possible safe
(an ayurvedic herbal preparation) prevention of COVID-19 pandemic among Completed prophylactic remedy for COVID-19
health care personnel
CTRI/2020/06/025527/Amrta karuna Clinical trial on immunity and antiviral for Interventional (randomized, The formulation was found to be
syrup quarantine patients of COVID-19 parallel group, active controlled immunomodulatory
Trial) Closed to recruitment
® ®
CTRI/2020/06/025556/Virulina along A clinical trial to know the effect of Virulina Interventional (randomized, The formulation was found to boost the
with standard treatment protocol along with standard treatment in COVID-19 parallel group, placebo immunity of the patients and help ease the
positive patients controlled Trial) Completed symptoms
CTRI/2020/06/025590/Astha 15 capsule A clinical trial to evaluate safety and efficacy of Interventional (randomized, A better recovery rate was observed
polyherbal capsule Astha-15 used as an add parallel group, placebo
on therapy with standard care of therapy as controlled Trial) Completed
an immunity booster in the suspected and
COVID-19 diagnosed patients
CTRI/2020/06/025592/Immunity kit Use of herbal medicine like tulsi, amruth Interventional (single arm Trial) Upon using the ayurvedic formulation as
(giloy), turmeric, ashwagandha as add on Completed add on treatment, the recovery was better in
treatment in COVID-19 patients terms of signs and symptoms of COVID-19
patients
CTRI/2020/06/026221/Arogya Intervention of ayurvedic medicine (arogya Interventional (randomized, The unani regimen was found to be effective
Kashayam-20 kashayam) in COVID-19 positive cases parallel group, active controlled against the mild symptoms of covid 19
(asymptomatic and mild symptomatic) Trial) Completed
CTRI/2020/06/026227/Khameera A study on unani regimen for prevention of Interventional (non- Improvement was found in immune status of
marwareed Tiryaq-e-Arba Unani joshanda/ high/moderate risk population of COVID-19 randomized, multiple arm Trial) covid patients
decoction behidana (Cydonia oblonga) Completed
3 gm, unnab (Zizyphus jujube) 5 in number,
sapistan (Cordia myxa) 9 in numbers
CTRI/2020/06/025801/Tab. Bresol and Role of herbal immunomodulators in mild Interventional (randomized, Use of herbal immunomodulators as add on
tab. Septilin COVID-19 confirmed cases parallel group, active controlled treatment, improved the recovery rate of
Trial) Completed COVID-19 patients
CTRI/2020/07/026337/Add-on The COVID-19 study with ayurveda add-on Interventional (randomized, Efficacy of treatment was measured in terms
personalized ayurveda intervention to to ICMR guideline parallel group trial) completed of average stay of patients in the hospital to
ICMR guideline on Covid-19 become covid negative
(Continued on following page)
Frontiers in Pharmacology | www.frontiersin.org 3 March 2021 | Volume 11 | Article 578970Ahmad et al. Indian Medicine against COVID 19
TABLE 1 | (Continued) Details of clinical trials completed on AYUSH drugs for COVID-19 (Source: www.ctri.nic.in).
Ctri No./Treatment details Study title Type of trial Remarks
(design of study)
Recruitment status
CTRI/2020/07/026371/1. Kabasura Kabasura kudineer, shakti drops and Interventional (Others) Better recovery rate was observed in terms
kudineer 2.Shakti drops 3.Turmeric plus turmeric plus in the management of Completed of signs and symptoms of stage 1 and 2 of
tablets COVID-19 COVID-19 cases on addition of ayurvedic
medicines, thereby improving the quality life
of stage 1 and 2 of COVID-19 patients
CTRI/2020/07/026433/1. Dashamula Effect of ayurveda medicine in COVID-19 mild Interventional (randomized, No adverse reaction was observed and
kwatha and pathyadi kwatha with trikatu symptoms parallel group, active controlled improvement in signs and symptoms
churna 2. Sansamani vati 3. AYUSH 64 4. Trial) Completed
Yastimadhu Ghanavati
CTRI/2020/07/026570/Cap. IP Safety and efficacy of ayurvedic capsule in Interventional (randomized, Improvement was observed in respiratory
mild to moderate COVID-19 infection parallel group Trial) Completed symptoms of covid patients
can be identified to combat the current deadly pandemic. In combination of modern and traditional therapy might reduce
view of the COVID-19 outbreak, the entire human race across the severity of the disease, intensity of symptoms, death rate, and
the globe is perturbed. While there is no medicine for COVID- side effects. Similar are the observations for Shuanghuanglian (A
19 as of now, it is imperative to take preventive measures such Chinese medicine) a liquid composed of a blend of honeysuckle,
as practicing self-hygiene, social distancing and boosting Chinese skullcap, and forsythia, which is claimed to have
immunity. Many safe traditional formulations of AYUSH, antiviral, antibacterial, and immunomodulatory effects (https://
which are well known immunity modulators, have been www.bioworld.com/). Since AYUSH encompasses five different
used for centuries in respiratory disorders and in allergic systems of medicine, rich in a variety of traditional formulations,
conditions. The Ministry of AYUSH (Govt of India) has it is likely to have a better chance than other systems to come up
listed out such formulations and recommended their use as with a satisfactory solution to the COVID-19 crisis.
a prophylactic measure in red zones, containment zones, as Ayurveda means ‘Science of life’. It provides a complete system
well as for corona warriors. Many of them are now under to have a long and healthy life. It is derived from the concepts of
clinical trial in COVID-19 patients (Table 1). “Dinacharya” - daily regimes and “Ritucharya” - seasonal regimes
Similarly, there are many medicinal plants indigenous to India to maintain a healthy life. Uplifting and maintaining the immunity
and used in the Indian Systems of Medicine which have been is duly emphasized across the Ayurveda’s classical scriptures.
reported as potent antiviral with immunomodulatory and anti- The Unani system of medicine, known as Greco-Arab
allergic/anti asthmatic activities. Many of these medicinal plants Medicine, is built on the four conditions of living (hot, sodden,
are also an integral part of several traditional formulations that frosty, and dry) and four humors of Hippocratic hypothesis
have been in use for a long time. namely, blood, yellow bile, dark bile, and mucus. Epidemics,
This review discusses the possible alternative strategies for the referred to as waba in the Unani system of medicine, are
management of the SARS-CoV-2 infection by reducing its thought to occur if any contagion or ajsam-i -khabitha, finds a
morbidity in patients as an adjuvant to modern therapy and place in air and water. Furthering the view, Ibn-e-Sina (980–1035
also by providing prophylactic management. Further, potential CE) stated that epidemics spread from one person to another, and
testing targets of botanicals from Indian medicinal plants need to one city to another ‘like a message’ (Sina, 1878).
be explored against SARS-CoV-2 infection and categorized on a AYUSH systems of medicine propagate general preventive
priority basis in view of their reported antiviral, measures aimed at preventing the spread of infection such as
immunomodulatory and other related activities. social distancing, hygiene and anti-septic measures (sanitization
of surroundings), improvement of immunity, and promotion of
general health (dietary modifications and herbal drugs). The
2 POTENTIAL TRADITIONAL INDIAN/ present article elucidates some traditional Indian AYUSH
AYUSH FORMULATIONS FOR THE formulations with proven antiviral, anti-asthmatic, and
immunomodulatory activities, however their role in
MANAGEMENT OF COVID-19 combating COVID-19 needs to be established. Clinical trials
There is plenty of data supporting the effectiveness of herbs in of AYUSH medicines like Ashwagandha, Yashtimadhu,
treating the viral infection. For instance, in controlling the Guduchi, Pippali, and AYUSH-64 on patients, health
contagious disease spread in the Guangdong Province of workers, and those working in high-risk areas have been
China during the 2003 SARS outbreak (Zhang et al., 2020). initiated in India by the Ministry of AYUSH, Ministry of
There are convincing pieces of evidence to establish that Health and Family Welfares, and the Council of Scientific
traditional Chinese medicine (TCM) has favorable effect in the and Industrial Research (CSIR) with the technical support of
treatment or prevention of SARS (Yang et al., 2020). A Indian Council of Medical Research (ICMR) (Table 1).
Frontiers in Pharmacology | www.frontiersin.org 4 March 2021 | Volume 11 | Article 578970Ahmad et al. Indian Medicine against COVID 19
TABLE 2 | AYUSH recommended prophylactic approach through Ayurvedic formulations. Ref: AYUSH Ministry of Health Corona Advisory-D.O. No. S. 16030/18/2019-
NAM; dated: 06th March, 2020. Ref: AYUSH Ministry of Health Corona Advisory -F.No. Z 25.23/09/2018–2020-DCC (AYUSH); dated: 24th April, 2020.
Name Composition Proof of activity References
of the formulation related to
COVID-19
Anuthaila Leptadenia reticulate (Retz.) Wight and Arn. (root/ A,C Pravansha et al. (2012), Mohanty et al. (2015)
stem bark)
Cedrus deodara (Roxb. ex D.Don) G.Don (stem) B Raghavendhar et al. (2019)
Vetiveria zizanioides (L.) Nash (root) B Lavanya et al. (2016)
Ocimum sanctum L. (leaves) A,B,C Goel et al. (2010), Ghoke et al. (2018), Soni et al. (2015)
Berberis aristata DC. (bark) A,B,C Yan et al. (2018), Wang et al. (2017), Kumar et al. (2016)
Glycyrrhiza glabra L. (root rhizome) A,B,C Mitra Mazumder et al. (2012), Ashraf et al. (2017), Patel et al. (2009)
Cyperus rotundus L. (rhizome) A,B,C Soumaya et al. (2013), Xu et al. (2015), Jin et al. (2011)
Asparagus racemosus Willd. (root) A Gautam et al. (2009)
Aegle marmelos (L.) Correa (stem bark) A,C Patel and Asdaq (2010), Kumari et al. (2014)
Solanum indicum L. (leaves) C Kaunda and Zhang (2019)
Solanum xanthocarpum Schrad. and Wendl (fruit) B Kumar and Pandey (2014)
Uraria picta (jacq.) DC. (whole plant) C Nagarkar et al. (2013)
Embelia ribes Burm.f. (fruit) B,C Mahendran et al. (2011)
Cinnamomum verum J.Presl. (bark) A,B,C Niphade et al. (2009), Brochot et al. (2017), Kandhare et al. (2013)
Elettaria cardamomum (L.) Maton (fruit) B Rahman et al. (2017)
Vitex negundo L. (leaves) A,B,C Lad et al. (2016), Kannan et al. (2012), Chattopadhyay et al. (2012)
Sesamum indicum L. (seed oil) A,C Khorrami et al. (2018), Nagpurkar and Patil (2017)
Agasthaya Aegle marmelos (L.) Correa (root/stem bark) A,C Patel and Asdaq (2010), Kumari et al. (2014)
hareetaki Oroxylum indicum (L.) Kurz (root/stem bark) B Zaveri et al. (2008)
Gmelina arborea Roxb. (root/stem bark) B Panda et al. (2017)
Stereospermum suaveolens (Roxb.) DC. (root/stem C Balasubramanian et al. (2010)
bark)
Premna mucronta Roxb. (root/stem bark) A,C Dianita and Jantan (2017)
Desmodium gangeticum (L.) DC. (whole plant) A Gulati et al. (2002)
Uraria picta (jacq.) DC. (whole plant) C Nagarkar et al. (2013)
Solanum indicum L. (whole plant) C Kaunda and Zhang (2019)
Solanum surattense Burm.f. (whole plant) C Kaunda and Zhang (2019)
Tribulus terrestis L. (whole plant) B,C Malik et al. (2018), Kang et al. (2017)
Mucuna pruriens (L.) DC. (seed) B,C Lampariello et al. (2012)
Convolvulus pluricaulis Choisy (whole plant) A,B,C Agarwal et al. (2014)
Hedychium spicatum Sm. (rhizome) A,C Uttara and Mishra (2009), Ghildiyal et al. (2012)
Sida cordifolia L. (root) A,C Tekade et al. (2008), Singh S. et al. (2011)
Piper chaba Hunter (fruit) C Sireeratawong et al. (2012)
Achyranthes aspera L. (root) A,B,C Narayan and Kumar (2014), Mukherjee et al. (2013), Khuda et al.
(2013)
Piper longum L. (root) A,B,C Tripathi et al. (1999), Jiang et al. (2013), Kaushik et al. (2012)
Plumbago zeylanica L. (root) B Gebre-Mariam et al. (2006)
Clerodendron serratum Spr. (root) A Juvekar et al. (2006)
Inula racemosa Hook.f. (root) A,C Mishra et al. (2016), Vadnere et al. (2009)
Hordeum vulgare L. (seed) C Gul et al. (2014)
Terminalia chebula Retz. (pulp) A,B,C Shivaprasad et al. (2006), Kesharwani et al. (2017), Haq et al. (2013)
Samshamani vati Tinospora cardifolia (Willd.) Miers (stem) A,B,C Alsuhaibani and Khan (2017), Pruthvish and Gopinatha (2018), Tiwari
et al. (2014)
AYUSH-64 Alstonia scholaris (L.) R.Br. (bark) A,B,C Iwo et al. (2000), Antony et al. (2014), Zhao et al. (2017)
Picrorhiza kurroa Royle ex Benth. (rhizome) A,B,C Sharma et al. (1994), Win et al. (2019), Sehgal et al. (2013)
Swertia chirayita (Roxb.) H.Karst. (whole plant) B,C Woo et al. (2019), Khan et al. (2012)
Caesalpinia crista L. (seed pulp) C Ramesh et al. (2014)
AYUSH kwath Ocimum sanctum L. (leaves) A,B,C Goel et al. (2010), Ghoke et al. (2018), Soni et al. (2015)
Cinnamomum verum J.Presl. (stem bark) A,B,C Niphade et al. (2009), Brochot et al. (2017), Kandhare et al. (2013)
Zingiber officinale Roscoe (rhizome) A,B,C Zhou et al. (2006), Chang et al. (2013), Khan et al. (2015)
Piper nigrum L. (fruit) A,B,C Majdalawieh and Carr (2010), Mair et al. (2016), Tasleem et al. (2014)
Note: A Immunomodulators; B Antiviral; C Anti-allergic/Anti-asthmatic/Anti-inflammatory/Respiratory disorders.
3 AYUSH RECOMMENDATIONS FOR of COVID-19. These different approaches are being followed by the
MANAGEMENT OF COVID-19 Hospitals as per their specialization, mainly as adjuvants to modern
medicine, which could be potentially relevant for COVID 19
Based on the different systems of Indian Medicine, separate treatment. Details of recommended formulations are described
recommendations have been issued from time to time from the below and depicted in Table 2 (Ayurveda), Table 3 (Unani) and
Ministry of AYUSH (Government of India) for the management Table 4 (Siddha).
Frontiers in Pharmacology | www.frontiersin.org 5 March 2021 | Volume 11 | Article 578970Ahmad et al. Indian Medicine against COVID 19
TABLE 3 | AYUSH recommended prophylactic approach through Unani formulation. Ref: AYUSH Ministry of Health Corona Advisory–D.O. No. S. 16030/18/2019- NAM;
dated: 06th March, 2020.
Name Composition Proof of activity References
of the formulation related to
COVID-19
Arq-e-Ajeeb Camphor B,C Chen et al. (2013), Ziment and Tashkin (2000)
Menthol B,C Taylor et al. (2020), Ziment and Tashkin (2000)
Thymol C Al-Khalaf (2013)
Asgandh safoof Withania somnifera (L.) Dunal (root) A,B,C Rasool and Varalakshmi (2006), Pant et al. (2012), Sahni and Srivastava
(1993)
Habb-e-Bukhar Cinchona officinale L. (bark) B Devaux et al. (2020)
Tinospora cordifolia (Willd.) Miers (stem) A,B,C Alsuhaibani and Khan (2017), Pruthvish and Gopinatha (2018), Tiwari et al.
(2014)
Bambusa bambos (L.) Voss (stem) A Sriraman et al. (2015)
Acacia arabica (Lam.) Willd. (gum) C Roqaiya et al. (2015)
Habb-e-Hindi zeeqi Aconitum chasmanthum Stapf ex Holmes (root) C Alamgeer et al. (2018)
Calotropis procera (Aiton) W.T.Aiton (root) A,C Bagherwal (2011), Arya and Kumar (2005)
Zingiber officinale Roscoe (rhizome) A,B,C Zhou et al. (2006), Chang et al. (2013), Khan et al. (2015)
Habb-e-Mubarak Myrica esculenta Buch.-Ham. ex D.Don (stem A,C Kabra et al. (2019)
bark)
Caesalpinia bonduc (L.) Roxb. (cotyledon) A,C Shukla et al. (2010), Arunadevi et al. (2015)
Khamira-e-Banafsa Viola odorata L. (flower) B,C Gerlach et al. (2019), Koochek et al. (2003)
Khameera Mytilus margaritiferus (pearl) A Khan et al. (2009), Beaulieu et al. (2013)
marwareed Bambusa bambos (L.) Voss (stem) C Muniappan and Sundararaj (2003)
Vateria indica L. (gum) B,C Meena and Ramaswamy (2015)
Santalum album L. (stem) B,C Paulpandi et al. (2012), Gupta and Chaphalkar (2016)
Rosa × damascena Mill. (flower) B,C Mahmood et al. (1996), Boskabady et al. (2011)
Laooq-e-Katan Linum usitatissimum L. (seed) A,C Liang et al. (2019), Rafieian-kopaei et al. (2017)
Laooq-e-Sapistan Cordia myxa L. (fruit) A,B,C Ali et al. (2015), Rashed (2014), Ranjbar et al. (2013)
Ziziphus jujuba Mill. (fruit) A,B,C Yu et al. (2016), Hong et al. (2015), Mesaik et al. (2018)
Viola odorata L. (flower) B,C Gerlach et al. (2019), Koochek et al. (2003)
Althea officinalis L. (seed) C Bonaterra et al. (2020)
Cassia fistula L. (seed) A,B,C Laxmi (2015), Indrasetiawan et al. (2019), Antonisamy et al. (2019)
Cassia angustifolia M. Vahl (leaves) A Jassim and Naji (2003)
Fraxinus ornus L. (flower) C Al-Snafi (2018)
Prunus amygdalus Batsch (seed oil) B,C Musarra-Pizzo et al. (2019), Masihuddin et al. (2019)
Roghan-e-Baboona Matricaria chamomilla L. (flower) A,C Amirghofran et al. (2000), Singh O. et al. (2011)
Sarbat-e sadr Bombyx mori (cocoons) A Soumya et al. (2019)
Ziziphus jujuba Mill. (fruit) A,B,C Yu et al. (2016), Hong et al. (2015), Mesaik et al. (2018)
Tachyspermum ammi (L.) Sprague (seed) A,B Shruthi et al. (2017), Roy et al. (2015)
Glycyrrhiza glabra L. (root) A,B,C Mitra Mazumder et al. (2012), Ashraf et al. (2017), Patel et al. (2009)
Foeniculum vulgare Mill. (fruit) C Rather et al. (2016)
Adhatoda vasica Nees (leaves) A,B,C Vinothapooshan and Sundar (2011), Singh et al. (2010), Gibbs (2009)
Onosma bracteatum Wall. (leaves) C Patel et al. (2011)
Malva sylvestris L. (seed) C Martins et al. (2017)
Hyssopus offloinalis L. (whole plant) B Behbahani (2009)
Ficus carica L. (fruit) A,B,C Patil et al. (2010), Camero et al. (2014), Abe (2020)
Cordia myxa L. (fruit) C Oza and Kulkarni (2017)
Papaver somniferum L. (flower) B,C Chattopadhyay and Naik (2007)
Onosma bracteatum Wall. (flower) C Patel et al. (2011)
Sharbat-e-Toot Morus nigra L. (fruit) A,C Lim and Choi (2019)
siyah
Triyaq-e-Araba Laurus nobilis L. (berries) A Aurori et al. (2016)
Bergenia ciliata (haw.) Sternb. (stem) A Rajbhandari et al. (2009)
Aristolochia indiaca L. (root) C Mathew et al. (2011)
Commiphora myrrha (Nees) Engl. (gum) C Su et al. (2015)
Note: AProvide the references Mallik and nayak (2014), Sengottuvelu et al. (2012), and Weili et al. (2011) Immunomodulators; B Antiviral; C Anti-allergic/Antiasthmatic/Anti-
inflammatory/Respiratory disorders.
3.1 Ayurvedic Approaches Cinnamomum verum J. Presl. stem barks, Zingiber officinale
3.1.1 AYUSH Kwath Roscoe rhizomes and Piper nigrum L. fruits. The formulation
Ministry of AYUSH promotes the use of AYUSH kwath, which is is sold in the market with different names like ‘AYUSH Kwath’,
a ready-made formulation for health promotion of the masses. ‘AYUSH Kudineer’ or ‘AYUSH Joshanda’. It is available in
The formulation is made of four herbs Ocimum sanctum L. leaves, powder and tablet forms in the market. These herbs are
Frontiers in Pharmacology | www.frontiersin.org 6 March 2021 | Volume 11 | Article 578970Ahmad et al. Indian Medicine against COVID 19
TABLE 4 | AYUSH recommended prophylactic approach through formulations of Siddha system of medicine. Ref: AYUSH Ministry of Health Corona Advisory–D.O. No. S.
16030/18/2019-NAM; dated: 06th March, 2020.
Name Composition Proof of activities References
of the formulation related to
COVID-19
Ahatodai manapagu Adhatoda vasica Nees (leaves) A,B,C Vinothapooshan and Sundar (2011), Singh et al. (2010), Gibbs
(siddha) (2009)
Saccharum officinarum L. C Cheavegatti-Gianotto et al. (2011)
Kabasura kudineer Zingiber officinale Roscoe (rhizome) A,B,C Zhou et al. (2006), Chang et al. (2013), Khan et al. (2015)
(siddha) Piper longum L. (fruit) A,B,C Tripathi et al. (1999), Jiang et al. (2013), Kaushik et al. (2012)
Syzygium aromaticum (L.) Merr. and L.M. Perry (fruit) A,C Dibazar et al. (2015), Chniguir et al. (2019)
Tragia involucrate L. (leaves) B,C Kumar et al. (2019), Alagar Yadav et al. (2015)
Anacyclus pyrethrum (L.) Lag. (root) A,B Sharma et al. (2010), Kumar et al. (2019)
Adhatoda vasica Nees (leaves) A,B,C Vinothapooshan and Sundar (2011), Singh et al. (2010), Gibbs
(2009)
Tinospora cordifolia (Willd.) Miers (stem) A,B,C Alsuhaibani and Khan (2017), Pruthvish and Gopinatha (2018),
Tiwari et al. (2014)
Andrographis paniculata (Burm.f.) Nees (whole plant) A,B,C Wang et al. (2010), Wintachai et al. (2015), Bao et al. (2009)
Sida acuta Burm.f. (root) C Arciniegas et al. (2017)
Cyperus rotundus L. (rhizome) A,B,C Soumaya et al. (2013), Xu et al. (2015), Jin et al. (2011)
Terminalia chebula Retz. (pulp) A,B,C Shivaprasad et al. (2006), Kesharwani et al. (2017), Haq et al.
(2013)
Nilavembu kudineer Andrographis paniculata (Burm.f.) Nees (whole plant) A,B,C Wang et al. (2010), Wintachai et al. (2015), Bao et al. (2009)
(siddha) Plectranthus vettiveroides (Jacob) N.P.Singh and A,B Kavinilavan et al. (2017)
B.D.Sharma (root)
Vetiveria zizanioides (L.) Nash (root) B Lavanya et al. (2016)
Zingiber officinale Roscoe (rhizome) A,B,C Zhou et al. (2006), Chang et al. (2013), Khan et al. (2015)
Piper Nigrum L. (fruit) A,B,C Majdalawieh and Carr (2010), Mair et al. (2016), Tasleem et al.
(2014)
Cyperus rotundus L. (rhizome) A,B,C Soumaya et al. (2013), Xu et al. (2015), Jin et al. (2011)
Santalum album L. (stem) B,C Paulpandi et al. (2012), Gupta and Chaphalkar (2016)
Trichosanthes cucumerina L. (whole plant) B,C Kumar et al. (2019), Arawwawala et al. (2010)
Mollugo cerviana (L.) Ser. (whole plant) A,B,C Ferreira et al. (2003), Jain et al. (2019), Sadique et al. (1987)
Note: A Immunomodulators; B Antiviral; C Anti-allergic/Antiasthmatic/Anti-inflammatory/Respiratory disorders.
reported to boost immunity (Carrasco et al., 2009; Niphade et al., 2012; Sehgal et al., 2013; Panda et al., 2017; Win et al., 2019; Woo
2009; Alsuhaibani and Khan, 2017; Bhalla et al., 2017) and are et al., 2019).
active remedies to various viral diseases (Mair et al., 2016; Ghoke
et al., 2018; Pruthvish and Gopinatha, 2018). 3.1.4 Agasthaya Hareetaki
Agastya Haritaki Rasayana is a popular ‘Avaleha kalpana’,
3.1.2 Samshamani Vati used in the management of various respiratory infection and
Samshamani vati (Guduchi ghana vati) is an ayurvedic comprises more than 15 herbal ingredients. Most of its
formulation used in all types of fevers. It is also used as an ingredients showed antiviral, anti-asthmatic, anti-
antipyretic and anti-inflammatory remedy (Patgiri et al., inflammatory, and immunomodulatory activities (Mouhajir
2014). Samshamani vati is made of aqueous extract of et al., 2001; Tripathi and Upadhyay, 2001; Balasubramanian
Tinospora cordifolia (Willd.) Miers (family et al., 2007; Vadnere et al., 2009; Patel and Asdaq, 2010;
Menispermaceae), and reported to be an immunomodulator Pathak et al., 2010; Jain et al., 2011; Kumar et al., 2011;
(More and Pai, 2011) due to the synergistic effect of the various Lampariello et al., 2012; Jiang et al., 2013). The above
compounds present. It is also effective in various viral diseases literature suggests the symptomatic management of
(Sachan et al., 2019). COVID-19 by Agastya Haritaki.
3.1.3 AYUSH-64 3.1.5 Anuthaila
AYUSH-64 tablet is composed of Alstonia scholaris (L.) R. Br. bark, Anuthaila consists of about twenty ingredients and out of them
Picrorhiza kurroa Royle ex Benth. rhizomes, Swertia chirayita (Roxb.) Leptadenia reticulate (Retz.) Wight and Arn. has been reported
H. Karst. whole plant, and Caesalpinia crista L. seed pulp. Because of in allergic response, treatment of asthma, bronchitis, and throat
its antimalarial activity, AYUSH-64 is considered to be effective trouble (Mohanty et al., 2017). Similarly, Ocimum sanctum L. is
among the high-risk coronavirus population. Researchers have recommended for a wide range of conditions including, cough,
reported that each of its constituents is effectively antiviral, anti- asthma, fever, and malaria (Cohen, 2014) and Sesamum
asthmatic, and immunoboosting (Sharma et al., 1994; Siddiqui et al., indicum L. oil for dry cough, asthma, migraine, and
Frontiers in Pharmacology | www.frontiersin.org 7 March 2021 | Volume 11 | Article 578970Ahmad et al. Indian Medicine against COVID 19
respiratory infections (Nagpurkar and Patil, 2017). There are reduces inflammation of the pharynx, tonsils, and irritation or
reports on S. indicum seeds with Tachyspermum ammi (L.) Sprague infection. The jelly like sticky mass of ripe fruit of Cordia myxa L.
seeds for dry cough, asthma, lung diseases, and common cold (Patil is the main ingredient, which has been reported as antiviral and
et al., 2008). On the basis of above literature, Anuthaila justifies its antitussive (Jamkhande et al., 2013). Another important
use in corona virus pandemic condition (Table 2). constituent is Ziziphus fruit, which contains betulinic acid.
Literature showed the down-regulation of IFN-γ level by
3.2 Unani Approaches betulinic acid in mouse lung, thus enhancing immunity and
3.2.1 Triyaq-e-Araba suggested as potential therapeutic agent for viral infections
Triyaq-e-Araba is an important Unani formulation used as a (Hong et al., 2015). Aqueous extract also reported increasing
detoxifying agent. It contains Laurus nobilis L. berries, Bergenia thymus and spleen indices as well as enhance the T-lymphocyte
ciliate (Haw.) Sternb. stem, Aristolochia indica L. roots and proliferation, hemolytic activity, and natural killer (NK) cell
Commiphora myrrha (Nees) Engl. It has been reported by several activity (Yu et al., 2016). Viola odorata L., one of its
authors as a potent antiviral agent (Aurori et al., 2016), including ingredients, suppresses the viral load (Gerlach et al., 2019).
against SARS-CoV (Loizzo et al., 2008). Further, B. ciliata is found to Hence, the literature supports the use of AYUSH formulation
be effective against the influenza virus-A and herpes simplex virus-1 Laooq-e-Sapistan in COVID-19.
(HSV-1) (Rajbhandari et al., 2003), whereas its active principal,
bergenin, has been found to be effective against hepatitis C virus 3.2.6 Sharbat-e-Sadar
(HCV) and HIV virus (Ahmad et al., 2018). On the basis of this Sharbat-e- Sadar is an Unani polyherbal syrup formulation and is
literature, Triyaq-e-Araba could be one of the effective antiviral widely used for common cold, cough and respiratory diseases.
medicine and certifies its use against COVID-19. Trachyspermum ammi (L.) Sprague, an important ingredient,
reported to neutralize antibodies for Japanese encephalitis virus
3.2.2 Roghan-e-Baboona (Roy et al., 2015), and a glycoprotein was found to proliferate
Roghan-e-Baboona is an Unani remedy utilized as an anti- B-cells (Shruthi et al., 2017). Adhatoda vasica Nees inhibits HIV-
asthmatic and for the treatment of inflammatory complaints. Protease (Singh et al., 2010), Bombyx mori was reported to
Flowers of Matricaria chamomilla L. are the main ingredient of increase immune responses against viral infection (Lü et al.,
Roghan-e-Baboona. It is composed of the flowers of M. 2018). Other ingredients such as Glycyrrhiza glabra L., Ficus
chamomilla, which is found effective for acute viral carica L., Onosma bracteatum Wall., and Ziziphus jujuba Mill.
nasopharyngitis (Srivastava et al., 2010), as well as for sore also possess the antiviral and immunomodulatory activities, as
throat (Kyokong et al., 2002). summarized in Table 5.
3.2.3 Arq-e-Ajeeb 3.2.7 Khameera Marwareed
Arq-e-Ajeeb is a liquid preparation that contains thymol, Khameera marwareed is a compound, sugar-based, semisolid
menthol, and camphor. Thymol is a promising candidate for Unani formulation used as an immunomodulator. It has been
topical application as an antiviral agent for herpetic infections reported to stimulate the immune system through T helper 1
(Lai et al., 2012; Sharifi-Rad et al., 2017). Menthol has been (Th1) type cytokine response and maintains the body in a
reported as an anti-inflammatory agent (Zaia et al., 2016). The healthier position to fight against viral infections (Khan et al.,
Unani physicians have a very successful history of treating Nazla 2009). Its ingredients showed powerful antiviral activities by
wabai (Swine flu) using Arq -e-Ajeeb. These studies support the inhibiting replication (Benencia and Courrèges, 1999).
use of Arq-e-Ajeeb for COVID-19.
3.2.8 Asgandh Safoof
3.2.4 Khamira-e-Banafsha Asgand (Withania somnifera (L.) Dunal) is a very popular Indian
Khamira-e-Banafsha is a semi-solid Unani formulation prepared medicinal plant. The root powder is used in the Unani system of
by adding decoction of flowers of Viola odorata L. to a base of medicine as an immunomodulator. It is reported that the root’s
sugar or sugar with honey and used for cold-cough as expectorant extract significantly increases the CD4+ and CD8+ counts (Bani et al.,
and for the treatment of ailments of respiratory system and chest 2006) and blood profile, especially WBC and platelet counts
diseases, bronchitis, whooping cough, fever, expectorant, (Agarwal et al., 1999). Aqueous suspension showed potent
antipyretic etc. Further, V. odorata has been reported to inhibitory activity toward mitogen-induced proliferative response
suppress the viral load and increase antiretroviral drug efficacy of T-lymphocytes and prevent SARS-CoV-2 entry by disturbing
(Gerlach et al., 2019), decrease the thickness of the alveolar wall, connections between viral S-protein receptor binding domain and
hemorrhage area, and alter the epithelial lining of bronchioles of host ACE2 receptor (Balkrishna et al., 2020). The above literature
the lungs (Koochek et al., 2003). The above literature supports its supports the preventive use of Asgandh safoof against COVID-19.
use for the management of COVID-19.
3.2.9 Habb-e-Bukhar
3.2.5 Laooq-e-Sapistan Habb-e-Bukhar is a polyherbal tablet formulation of Unani
Laooq-e-Sapistan is a semisolid sugar-based polyherbal Unani system of medicine, prescribed in elephantiasis and malarial
formulation extensively used by the masses in India for the fever. The main ingredient of Habb-e-Bukhar is cinchona
treatment of cold and cough, whooping cough, and phlegm. It bark. Its active constituent quinine is being used by some
Frontiers in Pharmacology | www.frontiersin.org 8 March 2021 | Volume 11 | Article 578970Frontiers in Pharmacology | www.frontiersin.org
Ahmad et al.
TABLE 5 | List of Indian Medicinal Plants/AYUSH drugs with proven immunomodulatory, antiviral and anti-allergic/anti-inflammatory/anti-asthmatic activity having potential for exploring against COVID 19 categorized for
prioritization on the basis of their earlier reports.
Category. Botanical name/Common name/Family/Part Immunomodulatory activity Anti-viral activity Anti-allergic/anti asthmatic/anti-
Sl no inflammatory/respiratory disorders
C1.1 Acacia catechu (L.f.) Aqueous and alcoholic extract increased Aqueous, hydroalcoholic and n-butanol extract Aqueous extract of leaves showed inhibitory
Willd./Khadira/Fabaceae/Leaves, phagocytic response showed by peritoneal showed anti HIV-1 activity by inhibiting viral effects on histamine synthesis in rat peritoneal as
bark, heartwood macrophages. The extracts inhibited TNF-α and protein and Tat IC50: 1.8 μg/ml Nutan et al. well as mast cells. Dose: 100 mg/kg Prasad
the production of NO, IL-10. Dose: 100 and (2013) et al. (2009), Negi and Dave (2010)
200 mg/kg Sunil et al. (2019)
C1.2 Adhatoda vasica Nees/Adusa/Acanthaceae/ Methanolic extract of leaves inhibit DTH Ethanolic leaf extract inhibit the activity of HIV- Alcoholic extract inhibited IgE-dependent
Leaves reactiveness, increased the percentage Protease. HIV-protease plays a significant part in basophil mediator release. Dose: 20 mg/kg
neutrophil adhesion, promoting increased the replication cycle. Singh et al. (2010) Gibbs (2009), Hossain and Hoq (2016)
phagocytic activity vis-à-vis increased
concentration of lytic enzymes for more effective
killing.Dose: 400 mg/kg Vinothapooshan and
Sundar (2011)
C1.3 Aegle marmelos (L.) Correa/Bael/Rutaceae/Root, Alcoholic extract stimulates immune system by Purified seselin showed inhibitory potential over Aqueous extract inhibit production of nitric oxide
stem bark, fruits acting through cellular and humoral multiple SARS-COV-2 targets and holds a high (NO) by rat peritoneal cells, anti-histamine effect,
immunity.Dose: 100 and 500 mg/kg Patel and potential to work effectively as a novel drug for and membrane stabilization activity. Dose:
Asdaq (2010) COVID-19. Nivetha et al. (2020) 200 mg/kg Kumari et al. (2014)
C1.4 Anacyclus pyrethrum (L.) Lag./Akkal kadha/ Petroleum ether extract showed cellular and Pyrethrin act as ligands to bind with viral proteins to -
Asteraaceae/Root humoral immunity.Dose: 50–100 mg/kg prevent the binding of host receptors preventing the
Sharma et al. (2010) fusion lead viral replication in COVID 19 Kumar et al.
(2019)
C1.5 Andrographis paniculata (Burm.f.) Nees/ Isolated compound of andrographolide modulate Alcoholic extract inhibit the viral titer in A549 cells Andrographolide attenuate allergic asthma by
9
Kalmegh/Acanthaceae/Leaves immune responses by regulating macrophage transfected with SRV. They showed the activity inhibition of the NF-kappaB signaling pathway.
phenotypic polarization and MAPK and PI3K through p38 MAPK/Nrf2 pathway.Dose: 50 μg/ Dose: 0.1, 0.5, and 1 mg/kg Bao et al. (2009)
signaling pathways regulate macrophage ml Churiyah et al. (2015), Wintachai et al. (2015)
polarization. Dose: 10 μg/ml (In vitro) and
1 mg/kg (In vivo) Wang et al. (2010)
C1.6 Carica papaya L./Papaya/Caricaceae/Leaves, Alcoholic extract of fruit pulp and seed enhanced Aqueous extract of the C. papaya leaves Alcoholic extract of leaves in mouse model of
fruits phagocytic activity of peritoneal macrophages is increases the expression of the envelope and ovalbumin- (OVA) induced allergic asthma down
correlated with T helper 1 cytokine response. NS1 proteins in DENV-infected THP-1 cells.IC50: regulates IL-4, IL-5, eotaxin, TNF-α, NF-ĸB, and
Interferon-gamma increases the phagocytosis 100 μg/ml Sharma N. et al. (2019) iNOS levels thus exhibits anti-inflammatory effect.
process.Dose: 0.11 g/ml extract every day Dose: 100 mg/kg Inam et al. (2017)
using a gastric cannula Amin et al. (2019)
C1.7 Cassia occidentalis L./Kasunda/Fabaceae/Aerial Isolated rhein suppresses the functional Alcoholic extract showed that the plant Isolated anthraquinone showed anti-asthmatic
part, seeds responses of the T- and B-lymphocytes and also possessed an anti-HIV property through potential by decreasing mRNA expression of
March 2021 | Volume 11 | Article 578970
suppresses lymphoproliferation in inhibition of viral reverse transcriptase Th1/Th2 cytokine in lung tissue. Dose: 250, 500
splenocytes.Dose: 10 μM Panigrahi et al. (2016) activity.IC50: >100 mg/ml Estari et al. (2012) and 2000 mg/kg Xu et al. (2018)
C1.8 Cocculus hirustus (L.) Diels/Patalagarudi/ Methanolic extract showed significantly Found effective against all strains of dengue virus The methanolic leaf extract showed significant
Indian Medicine against COVID 19
Menispermaceae/Whole plant enhanced specific and non-specific activity on and SARS CoV 2 in in vitro studies, hence under analgesic activity in mice as well as significant
various immune paradigm in cyclophosphamide phase 2 clinical trial as phytopharmaceutical drug anti- inflammatory activity using in vitro and in vivo
induced immunosuppresed animals.Dose: against COVID 19 at 12 centers. (https://www. rat models. Dose: 100 mg/kg Sengottuvelu
200 mg/kg Mallik and nayak (2014) clinicaltrialsarena.com/news/sun-pharma-covid- et al. (2012)
19-trial/)
C1.9 Cordia myxa L./Sapistan/Boraginaceae/Fruits Aqueous extract of C. myxa fruits significantly Dichloromethane, ethyl acetate, and methanol Hydroalcoholic extract inhibit the oxidant stress
increased the delayed type hypersensitivity stem extracts showed anti-viral potential against factors that lead to progression of colitis.Dose:
(DTH), mitotic index (MI) of bone marrow and HIV-1 using the syncytia formation assay. IC50: 100 mg/kg Ranjbar et al. (2013)
spleen cells Ali et al. (2015) 21.8 μg/ml Rashed (2014)
(Continued on following page)Frontiers in Pharmacology | www.frontiersin.org
Ahmad et al.
TABLE 5 | (Continued) List of Indian Medicinal Plants/AYUSH drugs with proven immunomodulatory, antiviral and anti-allergic/anti-inflammatory/anti-asthmatic activity having potential for exploring against COVID 19
categorized for prioritization on the basis of their earlier reports.
Category. Botanical name/Common name/Family/Part Immunomodulatory activity Anti-viral activity Anti-allergic/anti asthmatic/anti-
Sl no inflammatory/respiratory disorders
C1.10 Curcuma longa L./Haldi/Zingiberaceae/Rhizome Lyophilized turmeric was found to decrease Aqueous extract of C. longa suppressed the HBV Alcoholic extract of C. longa ameliorates food
spleen weight, decrease the proportion of CD4−, replication and the transcription of HBV genes in allergy by maintaining Th1/Th2 immune balance
CD8+ T cells, and decrease phagocytic activity. HepG2 cells which produce HBV particles. in ovalbumin challenged mice. Dose: 100 mg/kg
Dose: 1 and 2% (w/w) Kim et al. (2014). Dose: 200 mg/L and 500 mg/L Kim et al. Shin et al. (2015)
Polysaccharide fraction of aqueous extract of C. (2009). Isolated curcuminoids from aqueous
longa inhibiting the secretion of IL-12 and PGE2. extract of curcuma longa exhibited significant
Dose: 0.8–500 μg/ml Chandrasekaran et al. inhibitory activity against the neuraminidases
(2013) from novel influenza H1N1 (WT) and oseltamivir-
resistant novel H1N1 (H274Y mutant) expressed
in 293 T cells. IC50: 6.18 ± 0.64 to 40.17 ±
0.79 μg/ml Dao et al. (2012).
Virtual screening of curcumin and its analogue
found its activity SARS CoV 2 surface proteins
and is under clinical trial. (https://chemrxiv.org/
articles/Virtual screening of curcumin and its
analogs against the spike surface glycoprotein of
SARS-cov-2 and SARS-cov/12142383)
C1.11 Cynodon dactylon (L.) Pers./Doorva/Poaceae/ Fresh juice of the grass increased humoral Alcoholic dried extract showed virustatic and Chloroform extract of whole plant produces a
Whole plants antibody response upon antigen challenge, virucidal activity against porcine reproductive and bronchodilation via antimuscarinic calcium
significant increase in antibody titer in the respiratory syndrome virus (PRRSV) and also channel blocking activators and
haemagglutination antibody assay and plaque significantly inhibits replication of PRRSV. Dose: phosphodiesterase inhibition activity. Dose: 5,
10
forming cell assay. Dose: 250 and 500 mg/kg 0.78 mg/ml Pringproa et al. (2014) 10, 50 and 100 mg/kg Patel et al. (2013)
Mangathayaru et al. (2009)
C1.12 Jatropha curcas L./Euphorbiaceae/Leaves, roots Phytoconstituents of hydroalcoholic extract Successive extract of J. curcas was evaluated by Isolated jatrophacine showed anti-inflammatory
ameliorated both cellular and humoral antibody inhibition of HIV replication as determined by HIV potential by inhibiting production of nitric oxide in
response. Dose: 0.25, 0.5, 1 mg/kg Abd-Alla p24 antigen ELISA showed 100% inhibition by LPS-induced RAW 264.7 macrophages. IC50:
et al. (2009) methanolic and 97.19% inhibition by aqueous 0.53 μM Yang et al. (2019)
extract. IC50: 0.0255–0.4137 mg/ml (aqueous)
and 0.00073–0.1278 mg/ml (Methanolic)
Dahake et al. (2013)
C1.13 Mollugo cerviana (L.) Ser./Grishmasundara/ Alcoholic extracts increase NO release by Alcoholic extract exhibits antiviral properties for Hydroalcoholic extract inhibit the levels of lipid
Molluginaceae/Whole plant peritoneal cells. Dose: 25 μg/ml Ferreira et al. both chikungunya virus and dengue virus. Dose: peroxides, acid phosphatase, and gamma-
(2003) 1.8 mg/ml Jain et al. (2019) glutamyl transpeptidase activity. Dose: 1 mg/g
Sadique et al. (1987)
C1.14 Nigella sativa L./Kalonji/Ranunculaceae/Seeds Aqueous extract of N. sativa enhance the Nigellidine and α- hederin found to have the best Aqueous extract of seed showed sensory
March 2021 | Volume 11 | Article 578970
proliferative capacity of splenocytes and T potential to act as COVID-19 treatment in receptors mediating reflex bronchoconstriction
lymphocytes, suppression of IFNγ secretion from docking studies. (https://chemrxiv.org/articles/ and tachykinin receptor antagonists. Dose:
Indian Medicine against COVID 19
splenocytes. Dose: 10, 50, and 100 g/ml Identification of compounds from nigella sativa as 3.3% w/w extract Boskabady et al. (2003)
Majdalawieh et al. (2010) new potential inhibitors of 2019 novel corona
virus Covid-19 molecular docking study/
12055716/1)N. sativa seeds oil possesses a
striking antiviral effect against MCMV infection.
Dose: 100 mg/100 ml/mouse Umar et al.
(2016)
(Continued on following page)Frontiers in Pharmacology | www.frontiersin.org
Ahmad et al.
TABLE 5 | (Continued) List of Indian Medicinal Plants/AYUSH drugs with proven immunomodulatory, antiviral and anti-allergic/anti-inflammatory/anti-asthmatic activity having potential for exploring against COVID 19
categorized for prioritization on the basis of their earlier reports.
Category. Botanical name/Common name/Family/Part Immunomodulatory activity Anti-viral activity Anti-allergic/anti asthmatic/anti-
Sl no inflammatory/respiratory disorders
C1.15 Ocimum sanctum L./Tulsi/Lamiaceae/Leaves Aqueous extract of leaves showed regulation of Hydroalcoholic extract showed promising Alcoholic extracts showed anti-asthmatic
IL-2 production and exhibited leukocytosis and antiviral properties against H9N2 virus by potential through inflammatory mechanism by
augmentation of T& B cells. Dose: 250 mg/kg inhibition of a stage in viral intracellular inhibiting LTC4, LTA4 and COX-2 in HL-60 cell
Goel et al. (2010) multiplication and non-specific interference with lines and reduction in inflammation in asthma
virus-cell interactions. Dose: 135, 67, 33 mg/ mice model. IC50: 1–10 μg/mlDose:
0.1 ml Ghoke et al. (2018)Tulsinol and 100 mg/kg Soni et al. (2015)
dihydroeugenol have been found effective
against SARS CoV 2 in molecular docking
studies. (https://papers.ssrn.com/sol3/papers.
cfm abstract id 3554371)
C1.16 Phyllanthus emblica L./Amla/Phyllanthaceae/ Alcoholic extract of fruits stimulate B and T Fractionated alcoholic extract inhibit HIV reverse Alcoholic extract exhibits anti-inflammatory and
Fruits lymphocyte and restored the interleukin transcriptase activity. IC50: >100 mg/ml Estari anti-oxidant activity by protecting RAW264.7
production considerably. Dose: 10 mg to 1 mg/ et al. (2012) cells from oxidative damage by increasing
ml Sai Ram et al. (2002) glutathione content and total superoxide
dismutase activity, suppressing MDA content
and decreasing release of pro-inflammatory
mediators. IC50: 0.677 ± 0.029 mg/ml Li W.
et al. (2020)
C1.17 Solanum nigrum L./Makoi/Solanaceae/Seeds, Isolated polysaccharides of significant increment Chloroform extract decreased the expression or Petroleum ether extract of berries inhibits asthma
barriers in the percentage of CD4+ T lymphocyte and a function of HCV NS3 protease in a dose by inhibiting increase in leukocyte and eosinophil
decrease in the percentage of CD8+ T dependent manner and GAPDH remained count, protection against mast cell degranulation
11
lymphocyte of tumor-bearing mice peripheral constant. Dose: 100 μg/μL Javed et al. (2011) and resisting contraction due to presence of
blood. Dose: 90, 180, 360 mg/kg Li et al. (2009) β-sitosterol. Dose: 50, 100 and 200 mg/kg
Nirmal et al. (2012)
C1.18 Valeriana wallichii DC./Valerianaceae/Roots Alcoholic root extract inhibited HCV by binding Alcoholic extract and its fraction inhibit HCV by Crude extract showed protection against airway
with HCV NS5B protein.Dose: 250 μg/ml Ganta binding with HCV NS5B protein. Dose: 200 μg/ disorders through relax ion of the low K+
et al. (2017) ml Ganta et al. (2017) (25 mM)-induced contractions with a mild effect
on the contractions induced by high K+ (80 mM).
Dose: 0.03–3.0 mg/ml Khan and Gilani (2012)
C1.19 Vitex negundo L./Renuka/Verbanaceae/Leaves Hydroalcoholic extract of leaves of V. negundo Alcoholic extract of leaves inhibits HIV-1 reverse V. negundo leaf oil inhibit COX-2 without much
activate the phagocytic cells such as transcriptase activity in in vitro assay thus exhibits interfering COX-1 pathways. Dose: 500 μL/kg
macrophages and neutrophils. Dose: anti-HIV activity. Dose: 200 μg/ml Kannan et al. Chattopadhyay et al. (2012)
200 mg/kg Lad et al. (2016) (2012)
C1.20 Withania somnifera (L.) Dunal/Asgand/ Aqueous suspension of root showed potent Hydro-alcoholic root extract of W. somnifera Aqueous extract of withania root inhibit histamine
Solanaceae/Roots inhibitory activity toward mitogen induced showed antiviral properties against IBD virus by and 5-HT in early phase and prostaglandins in
March 2021 | Volume 11 | Article 578970
proliferative response of T-lymphocyte and cytopathic effect reduction assay. Dose: 25 μg/ delayed phase of inflammatory reaction. Dose:
delayed-type hypersensitivity reaction. Dose: ml Pant et al. (2012). Withanone and withaferin a 1000 mg/kg Sahni and Srivastava (1993)
Indian Medicine against COVID 19
1000 mg/kg Rasool and Varalakshmi (2006) have been found effective against SARS CoV 2 in
bioinformatics studies and asgandh extract is
under clinical trial. (https://www.researchsquare.
com/article/rs-17806/v1), (http://www.
bioinformation.net/016/97320630016411.pdf)
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